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Bone builder

Researchers exploit NCSA resources to develop a bone replacement material that uses the body's own tissues.

Imagine not eating solid foods for 12 years because you lost most of your mandible to cancer. Or being a soldier with a grotesquely disfigured face, the result of a roadside bomb that destroyed your maxilla. Rebuilding jaw bones to restore these individual's ability to function in daily activities and have a normal cosmetic appearance is one of the key applications targeted by a team of mechanical science and engineering researchers developing bone scaffolds. The team hopes to ultimately develop scaffolds for load-bearing defects, using a ceramic material with composition similar to bone, that can be customized to each patient's unique need.

Giving nature a boost

Bones are an amazing feat of Mother Nature's engineering: lightweight, yet strong and hard. Bone tissue is made of collagen and a calcium phosphate mineral called hydroxyapatite (HA). Collagen gives bone its toughness, HA provides strength and stiffness. Bone structure varies depending on the location in the body, as well as on the size and health of the individual. Mother Nature tailors bone to the demands placed on it, growing stronger with more use. For example, tennis players have markedly larger bones in their playing arm.

Just as a scaffold supports a construction worker, a bone scaffold serves to fill the space of the injured site and provide support during recovery. And like for construction, the scaffold must be matched to the job or problems can ensue.

The Illinois team is developing a scaffold made from synthetic HA that can be shaped or fabricated to replicate the bone it is replacing. Because HA is a ceramic, it currently is used sparingly in the clinic. The team is hoping to prove that by tailoring both the structure and the microstructure of the scaffolds they can greatly improve bone ingrowth and, as a result, extend HA's use to include large and load-bearing applications. The jaw bones are load-bearing bones owing to the forces they take from chewing. Jaw bones are also complicated bones as each person's facial shape is different, thus requiring a customized scaffold shape. Wagoner Johnson says success with facial bones should easily transfer to the load-bearing bones of the legs or other extremities.

A requirement for bone scaffolds is that the properties be similar to the bone they replace. Thus, the team is working to tailor the scaffold's structural properties. But the structure, and therefore properties, of bone vary from place to place in the body, making this a challenging task. The scaffold the team designed has rods in an orthogonal, or checkered-like, pattern allowing bone tissue to grow in the spaces between the rods comprising the scaffold. Over time the scaffold dissolves and new bone tissue grows to take its place, resulting in a repair that is completely natural bone.

"Bone needs mechanical signals for it to grow properly," explains Wagoner Johnson. "If it receives the signal that something stiffer is there supporting the load then it will think it is not needed and will resorb, and that can cause problems." Think hip replacements, she says. Metallic artificial hip implants are stiffer than the bone they replace; bone surrounding the implant can resorb leaving space between the implant and the bone in which it is placed. After years of use and constant loading, the artificial hip has to be replaced as it may no longer fit the space nor function properly.

Wagoner Johnson says you also need pores of a particular range in size (hundreds of microns) for bone tissue to grow in; if the pores are too small new bone tissue won't grow in properly and if the pores are too big the structure will be too weak. The team found they can tailor the microstructure of the scaffold rods and that adding porosity to the rods improves new bone tissue growth.

Computer-aided testing

The team turned to NCSA and the research value of simulations to test and improve their scaffold design and determine how properties change when bone grows into the scaffold. "If we can change the structures, and therefore the properties, easily in a model, then we can investigate more easily whether a particular scaffold structure would be appropriate for a specific bone in the body or a specific patient," says Wagoner Johnson.

The team set out to model the elastic behavior, or stiffness, of the porous scaffolds plus composites of the scaffolds with different amounts of ingrown bone. The mechanical properties are usually experimentally determined after in vivo bone growth, but this is a lengthy and expensive process. However, the periodic structure, or repeating structure, of the scaffolds made representing the scaffold by one repeating unit, or representative volume element (RVE), convenient and computationally cheap. The main question, then, was how to represent the bone, which can have very different structure in different places in the body.

Using NCSA's recently retired Tungsten cluster, the team approximated the morphology of bone they'd observed from studies and put that into their scaffold, creating a very simple model to predict the effective elastic properties of HA scaffold/bone composites using RVE and finite element analysis. The team then modified the properties of the scaffold and altered its geometry to obtain information on how the changes affected the composite properties.

Two bone geometries that were very different geometrically were generated and several scaffolds were evaluated. Results showed the bone geometry actually had little influence on the effective elastic properties of the composites for the scaffolds considered. The team says the implication is that such properties can be estimated by measuring the volume fraction of bone using a non-destructive method like micro-CT and the simple RVE model, thus reducing the cost of and time required for scaffold evaluation, and evaluation of scaffolds with ingrown bone.

In fact, by using a model the team hopes to reduce the number of in vivo studies their project requires. To their knowledge, they are the first researchers to use in vivo experimental data to formulate a model of bone morphology and also the first to have examined morphology as a variable in scaffold/bone composite properties. And unlike other work, the geometries and volumes of bone they used represented an intermediate time point rather than just an initial and end point. The team's work is detailed in a paper submitted to Acta Biomaterialia.

Coming one day to orthopedists and oral surgeons

Wagoner Johnson says the idea is "that we will be able to make site-specific implants from these scaffolds." Currently, the team makes a larger scaffold and machines out simple shapes, such as cylinders, for their studies. "But we'd like to get to the point where can make these scaffolds for a patient-specific defect based on the patient's CT scans." Thanks to computer modeling, that day will come sooner than they thought. But not soon enough for the patients with very large and load-bearing bone defects whose form and function could be restored using this technology.